Study 1: Narcolepsy and BMI. Several cross-sectional studies have suggested that subjects with narcolepsy have increased BMI and insulin resistance. These subjects exhibit a decrease in CSF orexin levels, which has been pathogenetically linked to the clinical manifestations of this disease. The primary objectives of an on-going study is to determine whether hypocretin-deficient subjects with narcolepsy have lower energy expenditure and lower circulating levels of leptin compared to healthy matched controls. This is a cross-sectional, case-controlled study of energy expenditure in subjects with narcolepsy, who will be matched on a one-to-one basis with healthy, non-narcoleptic subjects used as controls. Outcome parameters include energy expenditure, as well as various endocrine parameters including leptin and orexin levels. The main analyses of the study will be to determine differences in mean energy expenditure and leptin levels. A metanalysis of the literature on this topic is in press [Sonbolian 2005] and a research protocol has been submitted to the NIDDK IRB. Study 2: Sleep extension in obese, sleep-deprived subjects. Obesity and chronic sleep deprivation have both become increasingly pervasive medical problems in recent years. As summarized in a recent editorial [Cizza 2005], average sleep time has decreased over the last century by 2 hours. Chronically sleeping less has been associated with endocrine and metabolic health risks including glucose intolerance, cardiovascular disease, and mortality. The possibility that the current epidemic of obesity and metabolic health risks may be partially related to insufficient sleep is now being recognized. A multidisciplinary, multi-institute Investigators Meeting was held on campus in January 2005 to finalize the design of the Sleep Extension Study. The study protocol has since passed scientific review and is now submitted to the IRB. The objective of this upcoming study is to test whether increasing sleep time in chronically sleep-deprived, obese subjects, would decrease body weight in these subjects. This is a randomized, controlled clinical trial of additional sleep per night (Intervention Group) or additional quiet time in bed (Control Group). The main analysis of the study will be to determine if an additional 90 minutes of sleep will decrease the prevalence of metabolic syndrome or of its components in chronically sleep deprived obese subjects.